Patient-derived xenografts recapitulate molecular features of human uveal melanomas

Cécile Laurent, David Gentien, Sophie Piperno-Neumann, Fariba Némati, André Nicolas, Bruno Tesson, Laurence Desjardins, Pascale Mariani, Audrey Rapinat, Xavier Sastre-Garau, Jérôme Couturier, Philippe Hupé, Leanne de Koning, Thierry Dubois, Sergio Roman-Roman, Marc Henri Stern, Emmanuel Barillot, J. William Harbour, Simon Saule, Didier Decaudin

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We have previously developed a new method for the development and maintenance of uveal melanoma (UM) xenografts in immunodeficient mice. Here, we compare the genetic profiles of the primary tumors to their corresponding xenografts that have been passaged over time. The study included sixteen primary UMs and corresponding xenografts at very early (P1), early (P4), and late (P9) in vivo passages. The tumors were analyzed for mutation status of GNAQ, GNA11, GNAS, GNA15, BAP1, and BRAF, chromosomal copy number alterations using Affymetrix GeneChip® Genome-Wide Human SNP6.0 arrays, gene expression profiles using GeneChip® Human Exon 1.0 ST arrays, BAP1 mRNA and protein expression, and MAPK pathway status using Reverse Phase Protein Arrays (RPPA). The UM xenografts accurately recapitulated the genetic features of primary human UMs and they exhibited genetic stability over the course of their in vivo maintenance. Our technique for establishing and maintaining primary UMs as xenograft tumors in immunodeficient mice exhibit a high degree of genetic conservation between the primary tumors and the xenograft tumors over multiple passages in vivo. These models therefore constitute valuable preclinical tool for drug screening in UM.

Original languageEnglish (US)
Pages (from-to)625-636
Number of pages12
JournalMolecular Oncology
Volume7
Issue number3
DOIs
StatePublished - Jun 2013
Externally publishedYes

    Fingerprint

Keywords

  • Gene expression profiling
  • Genome profiling
  • GNAQ/GNA11/BAP1 mutations
  • RPPA
  • Uveal melanoma
  • Xenografts

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Medicine

Cite this

Laurent, C., Gentien, D., Piperno-Neumann, S., Némati, F., Nicolas, A., Tesson, B., Desjardins, L., Mariani, P., Rapinat, A., Sastre-Garau, X., Couturier, J., Hupé, P., de Koning, L., Dubois, T., Roman-Roman, S., Stern, M. H., Barillot, E., Harbour, J. W., Saule, S., & Decaudin, D. (2013). Patient-derived xenografts recapitulate molecular features of human uveal melanomas. Molecular Oncology, 7(3), 625-636. https://doi.org/10.1016/j.molonc.2013.02.004